WordNet

the 4th letter of the Roman alphabet (同)d
a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

deuteriumの化学記号
=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/20 07:23:09」(JST)

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D₃ dopamine receptor is a protein that in humans is encoded by the DRD3 gene.^[1]^[2]

This gene encodes the D₃ subtype of the dopamine receptor. The D₃ subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions. It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease.^[3] Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD).^[2]

D₃ agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.^[4]^[5]

Ligands

Agonists

trans-N-{4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]cyclohexyl}-3-methoxybenzamide, full agonist, > 200-fold binding selectivity over D₄, D₂, 5-HT_1A, and α1-receptors^[6]
(-)-7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol^[7]
5-OH-DPAT
7-OH-DPAT
8-OH-PBZI (cis-8-Hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1H-benz[e]indole)
Apomorphine (non-selective dopamine agonist)
Bromocriptine (non-selective dopamine agonist)
Captodiame
CJ-1639^[8]
compound R,R-16: 250x binding selectivity over D₂^[9]
Dopamine (endogenous agonist)
ES609
FAUC 54
FAUC 73
PD-128,907
PF-219,061 (extremely selective) ^[10]
PF-592,379^[11]
Piribedil^[12] (non-selective dopamine agonist)
Pramipexole (non-selective dopamine agonist)
Quinelorane (also D2 agonist)
Quinpirole (also D2 agonist)
Ropinirole (non-selective dopamine agonist)
Rotigotine (non-selective dopamine agonist)

Partial agonists

Aripiprazole (non-selective)
BP-897^[13]
Buspirone (non-selective)
CJB 090
CJ-1037 (extremely selective) ^[14]
FAUC 460 (highly selective) ^[15]
FAUC 346 (highly selective)^[16]
Pardoprunox (non-selective)
Roxindole (possibly a partial agonist at the D3 autoreceptors, non-selective)
OS-3-106
UH-232
WW-III-55

Antagonists

Most Antipsychotics
Amisulpride (non-selective)
Cyproheptadine (non-selective)
PG 01037 ^[17]^[18]
Domperidone (peripheral D₂ and D₃ antagonist)
FAUC 365, silent antagonist, subtype selective^[16]
GR-103,691
GSK598809 (highly selective)
Haloperidol (non-selective)
N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides^[19]
Nafadotride
NGB-2904^[20]
PNU-99,194 (moderately selective over D2)
Raclopride (also D2 antagonist)
S-14,297 (selective)
S33084
SB-277011-A, selective D₃ antagonist, 80x selectivity over D₂ with no partial agonist effects, used in drug addiction research as a potential therapy for addiction to several different drugs
SR 21502 (highly selective)
Sulpiride (also D2 antagonist)
U99194
YQA14 (high affinity and selectivity)
Risperidone

Interactions

Dopamine receptor D₃ has been shown to interact with CLIC6^[21] and EPB41L1.^[22]

References

^ Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C, Schwartz JC, Berger R (Oct 1991). "Chromosomal localization of the human D3 dopamine receptor gene". Hum Genet 87 (5): 618–20. doi:10.1007/bf00209024. PMID 1916765.
^ ^a ^b "Entrez Gene: DRD3 dopamine receptor D3".
^ Joyce JN, Millan MJ (February 2007). "Dopamine D3 receptor agonists for protection and repair in Parkinson's disease.". Current Opinion in Pharmacology 7 (1): 100–5. doi:10.1016/j.coph.2006.11.004. PMID 17174156.
^ Breuer ME, Groenink L, Oosting RS, Buerger E, Korte M, Ferger B, Olivier B (August 2009). "Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats". European Journal of Pharmacology 616 (1-3): 134–40. doi:10.1016/j.ejphar.2009.06.029. PMID 19549514.
^ Bertaina-Anglade V, La Rochelle CD, Scheller DK (October 2006). "Antidepressant properties of rotigotine in experimental models of depression". European Journal of Pharmacology 548 (1-3): 106–14. doi:10.1016/j.ejphar.2006.07.022. PMID 16959244.
^ Leopoldo M, Lacivita E, Colabufo NA, Berardi F, Perrone R (2006). "Synthesis and binding profile of constrained analogues of N-[4-(4-arylpiperazin-1-yl)butyl]-3-methoxybenzamides, a class of potent dopamine D3 receptor ligands". J. Pharm. Pharmacol. 58 (2): 209–18. doi:10.1211/jpp.58.2.0008. PMID 16451749.
^ Biswas S, Zhang S, Fernandez F, Ghosh B, Zhen J, Kuzhikandathil E, Reith ME, Dutta AK (2008). "Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol analogues: identification of a high-affinity D₃-preferring agonist with potent in vivo activity with long duration of action". J. Med. Chem. 51 (1): 101–17. doi:10.1021/jm070860r. PMID 18072730.
^ Chen J, Collins GT, Levant B, Woods J, Deschamps JR, Wang S (August 2011). "CJ-1639: A Potent and Highly Selective Dopamine D3 Receptor Full Agonist". ACS Med Chem Lett 2 (8): 620–625. doi:10.1021/ml200100t. PMID 22125662.
^ Peglion JL, Poitevin C, Mannoury La Cour C, Dupuis D, Millan MJ (2009). "Modulations of the amide function of the preferential dopamine D3 agonist (R,R)-S32504: Improvements of affinity and selectivity for D3 versus D2 receptors". Bioorg. Med. Chem. Lett. 19 (8): 2133–8. doi:10.1016/j.bmcl.2009.03.015. PMID 19324548.
^ Blagg J, Allerton CM, Batchelor DV, Baxter AD, Burring DJ, Carr CL, Cook AS, Nichols CL, Phipps J, Sanderson VG, Verrier H, Wong S (2007). "Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route". Bioorg. Med. Chem. Lett. 17 (24): 6691–6. doi:10.1016/j.bmcl.2007.10.059. PMID 17976986.
^ Collins GT, Butler P, Wayman C, Ratcliffe S, Gupta P, Oberhofer G, Caine SB (2012). "Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in drug self-administration and drug discrimination in rats". Behavioural Pharmacology 23 (3): 280–291. doi:10.1097/FBP.0b013e3283536d21. PMC 3365486. PMID 22470105.
^ Cagnotto A, Parotti L, Mennini T (October 1996). "In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study". Eur. J. Pharmacol. 313 (1-2): 63–7. doi:10.1016/0014-2999(96)00503-1. PMID 8905329.
^ Spiller K, Xi ZX, Peng XQ, Newman AH, Ashby CR, Heidbreder C, Gaál J, Gardner EL (March 2008). "The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats". Psychopharmacology 196 (4): 533–42. doi:10.1007/s00213-007-0986-6. PMID 17985117.
^ Chen J, Collins GT, Zhang J, Yang CY, Levant B, Woods J, Wang S (2008). "Design, synthesis, and evaluation of potent and selective ligands for the dopamine 3 (D3) receptor with a novel in vivo behavioral profile". J. Med. Chem. 51 (19): 5905–8. doi:10.1021/jm800471h. PMC 2662387. PMID 18785726.
^ Dörfler M, Tschammer N, Hamperl K, Hübner H, Gmeiner P (2008). "Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies". J. Med. Chem. 51 (21): 6829–38. doi:10.1021/jm800895v. PMID 18834111.
^ ^a ^b Bettinetti L, Schlotter K, Hübner H, Gmeiner P (2002). "Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D₃ receptor antagonists and partial agonists". J. Med. Chem. 45 (21): 4594–7. doi:10.1021/jm025558r. PMID 12361386.
^ Grundt P, Carlson EE, Cao J, Bennett CJ, McElveen E, Taylor M, Luedtke RR, Newman AH (2005). "Novel heterocyclic trans olefin analogues of N-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as selective probes with high affinity for the dopamine D3 receptor". J. Med. Chem. 48 (3): 839–48. doi:10.1021/jm049465g. PMID 15689168.
^ Mason CW, Hassan HE, Kim KP, Cao J, Eddington ND, Newman AH, Voulalas PJ (12 March 2010). "Characterization of the Transport, Metabolism, and Pharmacokinetics of the Dopamine D3 Receptor-Selective Fluorenyl- and 2-Pyridylphenyl Amides Developed for Treatment of Psychostimulant Abuse". Journal of Pharmacology and Experimental Therapeutics 333 (3): 854–864. doi:10.1124/jpet.109.165084. PMID 20228156.
^ Newman AH, Grundt P, Cyriac G, Deschamps JR, Taylor M, Kumar R, Ho D, Luedtke RR (2009). "N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists ( parallel) ( perpendicular)". J. Med. Chem. 52 (8): 2559–70. doi:10.1021/jm900095y. PMC 2760932. PMID 19331412.
^ Xi ZX, Gardner EL (2007). "Pharmacological actions of NGB 2904, a selective dopamine D3 receptor antagonist, in animal models of drug addiction". CNS Drug Reviews 13 (2): 240–59. doi:10.1111/j.1527-3458.2007.00013.x. PMID 17627675.
^ Griffon N, Jeanneteau F, Prieur F, Diaz J, Sokoloff P (2003). "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors". Brain Res. Mol. Brain Res. 117 (1): 47–57. doi:10.1016/S0169-328X(03)00283-3. PMID 14499480.
^ Binda AV, Kabbani N, Lin R, Levenson R (2002). "D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N". Mol. Pharmacol. 62 (3): 507–13. doi:10.1124/mol.62.3.507. PMID 12181426.

External links

"Dopamine Receptors: D₃". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Receptors, Dopamine D3 at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

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1. インスリン受容体の構造および機能 structure and function of the insulin receptor
2. 甲状腺ホルモンの作用 thyroid hormone action
3. 免疫不全症を引き起こすCD3／T細胞受容体複合体疾患 cd3 t cell receptor complex disorders causing immunodeficiency
4. T細胞受容体の遺伝学 t cell receptor genetics
5. T細胞受容体シグナル伝達 t cell receptor signaling

English Journal

The inhibitory glutathione transferase M2-2 binding site is located in divergent region 3 of the cardiac ryanodine receptor.

Liu D, Hewawasam R, Karunasekara Y, Casarotto MG, Dulhunty AF, Board PG.SourceJohn Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT 2601, Australia.
Biochemical pharmacology.Biochem Pharmacol.2012 Jun 1;83(11):1523-9. Epub 2012 Mar 1.
The muscle-specific glutathione transferase GSTM2-2 modulates the activity of ryanodine receptor (RyR) calcium release channels: it inhibits the activity of cardiac RyR (RyR2) channels with high affinity and activates skeletal RyR (RyR1) channels with low affinity. The C terminal domain of GSTM2-2 (
PMID 22406107

Affinity and selectivity of [(11) C]-(+)-PHNO for the D3 and D2 receptors in the rhesus monkey brain in vivo.

Gallezot JD, Beaver JD, Gunn RN, Nabulsi N, Weinzimmer D, Singhal T, Slifstein M, Fowles K, Ding YS, Huang Y, Laruelle M, Carson RE, Rabiner EA.SourcePET Center, Department of Diagnostic Radiology, Yale University, New Haven, Connecticut.
Synapse (New York, N.Y.).Synapse.2012 Jun;66(6):489-500. doi: 10.1002/syn.21535. Epub 2012 Feb 24.
Although [(11) C]-(+)-PHNO has enabled quantification of the dopamine-D3 receptor (D3R) in the human brain in vivo, its selectivity for the D3R is not sufficiently high to allow us to disregard its binding to the dopamine-D2 receptor (D2R). We quantified the affinity of [(11) C]-(+)-PHNO for the D2R
PMID 22213512

Japanese Journal

胆汁酸代謝とビタミンD受容体

槇島誠
ビタミン 85(2), 47-56, 2011-02-25
… Nuclear receptors belonging to the NR1H and NR1I subfamilies, including vitamin D receptor (VDR, NR1I1), control cholesterol and bile acid metabolism. … VDR, a receptor for 1,25-dihydroxyvitamin D_3(1,25(OH)_2D_3), acts as a bile acid receptor with specificity for the secondary bile acid LCA and its derivatives. … VDR acts as a bile acid sensor as well as an endocrine receptor for vitamin D signaling. …
NAID 110008460669

The Vitamin D3 1alpha-Hydroxylase Gene and Its Regulation by Active Vitamin D3

TAKEYAMA Ken-ichi,KATO Shigeaki
Bioscience, biotechnology, and biochemistry 75(2), 208-213, 2011-02-23
… Most of these actions are mediated by transcriptional regulation of target genes through vitamin D receptor (VDR), a member the steroid/thyroid hormone receptor superfamily. … The active form of vitamin D, 1α,25(OH)2D3, derived by vitamin D3 1alpha hydroxylase, 1α(OH)ase in renal proximal tubule cells is a ligand for VDR. …
NAID 10027897347

「D3受容体」

Dopamine receptor D3
	Dopamine D3 receptor with Eticlopride(PDB 3PBL)
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	3PBL
Identifiers
Symbols	DRD3 ; D3DR; ETM1; FET1
External IDs	OMIM: 126451 MGI: 94925 HomoloGene: 623 IUPHAR: 216 ChEMBL: 234 GeneCards: DRD3 Gene
Gene ontology
Molecular function	• dopamine neurotransmitter receptor activity, coupled via Gi/Go; • protein binding; • drug binding; • G-protein coupled amine receptor activity; • protein domain specific binding; • D1 dopamine receptor binding; • dopamine binding;
Cellular component	• plasma membrane; • integral component of plasma membrane; • endocytic vesicle; • cell projection; • apical part of cell;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • synaptic transmission, dopaminergic; • response to amphetamine; • regulation of blood volume by renin-angiotensin; • G-protein coupled receptor internalization; • cellular calcium ion homeostasis; • G-protein coupled receptor signaling pathway; • adenylate cyclase-activating dopamine receptor signaling pathway; • negative regulation of adenylate cyclase activity; • adenylate cyclase-inhibiting dopamine receptor signaling pathway; • synaptic transmission; • sensory perception of chemical stimulus; • learning or memory; • learning; • locomotory behavior; • positive regulation of cell proliferation; • visual learning; • positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway; • regulation of dopamine secretion; • regulation of lipid metabolic process; • regulation of cAMP metabolic process; • negative regulation of sodium:proton antiporter activity; • positive regulation of cytokinesis; • circadian regulation of gene expression; • response to histamine; • social behavior; • gastric emptying; • positive regulation of renal sodium excretion; • regulation of multicellular organism growth; • response to cocaine; • dopamine metabolic process; • response to drug; • response to morphine; • regulation of circadian sleep/wake cycle, sleep; • response to ethanol; • negative regulation of blood pressure; • positive regulation of mitotic nuclear division; • positive regulation of transcription from RNA polymerase II promoter; • acid secretion; • behavioral response to cocaine; • negative regulation of oligodendrocyte differentiation; • arachidonic acid secretion; • negative regulation of protein secretion; • musculoskeletal movement, spinal reflex action; • regulation of dopamine uptake involved in synaptic transmission; • negative regulation of protein kinase B signaling; • prepulse inhibition; • negative regulation of dopamine receptor signaling pathway; • positive regulation of dopamine receptor signaling pathway; • regulation of locomotion involved in locomotory behavior;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;